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Fig. 2. The Hourglass model of NC induction: upstream and downstream of Pax3/Zic1. (A) General presentation of the "Hourglass model" for NB/NC-GRN, divided into a neural border module upstream of the activation of the two essential TFs Pax3 and Zic1, and a downstream module, describing Pax3 and Zic1 targets in subsequent NC induction. (B) Through a combination of Wnt, FGF and modulated BMP signals, NB-TFs are activated and mutually enhance each other's expression, creating a feed-forward NB stabilization loop, culminating with the robust and balanced activation of Pax3 and Zic1. (C) In turn, the balanced expression of Pax3 and Zic1 is necessary and sufficient to trigger all downstream aspects of NC development. The Pax3/Zic1-dependent GRN presented here has been validated in animal caps assays in vitro and frog whole embryos in vivo. The main regulations are shown, including the direct activation of the EMT-TFs snail2 and twist1 (ets1, also direct target EMT-TF is not shown). Direct regulations are shown with solid lines, other regulatory connections with dashed lines. References: Bonano et al. (2008); Marchal et al. (2009); Li et al. (2009); Gutkovich et al., 2010; Bae et al. (2014); Plouhinec et al. (2014).

Image published in: Pla P and Monsoro-Burq AH (2018)

Copyright © 2018. Image reproduced with permission of the Publisher, Elsevier B. V.

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